Differential regulation of the Oct-3/4 gene in cell culture model systems that parallel different stages of mammalian development

Sunil Kumar Mallanna, Brian Boer, Michelle Desler, Angie Rizzino

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Oct-3/4 is an essential transcription factor that regulates stem cell fate during embryogenesis. Previous reports have shown that the Oct-3/4 gene utilizes different enhancers to regulate its expression as development proceeds. However, the cis-elements contributing to the differential activity of these enhancers require further study. Here, we investigated the function of the HMG/POU cassette and LRH-1 site present in the distal enhancer (DE) and the proximal enhancer, respectively. F9 and P19 EC cells were the focus of this study because their differential utilization of Oct-3/4 enhancers parallels the use of these enhancers during different stages of development. We determined that the LRH-1 site functions as a positive and a negative cis-regulatory element in P19 and F9 EC cells, respectively. Furthermore, we determined that the HMG/POU cassette in the DE strongly activates the Oct-3/4 promoter in F9 cells, but is a much weaker positive regulatory element in P19 cells. Given that HMG/POU cassettes play key roles in the regulation of at least seven essential genes, the Oct-3/4 HMG/POU cassette was examined more closely by focusing on Sox2, which can bind to HMG/POU cassettes. Although chromatin immunoprecipitation demonstrated that Sox2 binds to the Oct-3/4 gene equally well in both EC cell lines, tethering Sox2 to the region of the HMG/POU cassette only activated the Oct-3/4 promoter in F9 EC cells. These and other findings suggest that the differential activity of the HMG/POU cassette of the Oct-3/4 gene in EC cells is due to differential action of Sox2 and its associated co-factors.

Original languageEnglish (US)
Pages (from-to)1247-1257
Number of pages11
JournalMolecular Reproduction and Development
Volume75
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • Differentiation
  • Enhancer
  • Oct-3/4
  • Sox2
  • Stem cells

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

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